Discrete analysis of camelid variable domains: sequences, structures, and in-silico structure prediction.

Autor: Melarkode Vattekatte A; Biologie Intégrée du Globule Rouge UMR_S1134, Inserm, Univ. Paris, Univ. de la Réunion, Univ. des Antilles, Paris, France.; Laboratoire d'Excellence GR-Ex, Paris, France.; Faculté des Sciences et Technologies, Saint Denis, La Réunion, France.; Institut National de la Transfusion Sanguine (INTS), Paris, France., Shinada NK; Biologie Intégrée du Globule Rouge UMR_S1134, Inserm, Univ. Paris, Univ. de la Réunion, Univ. des Antilles, Paris, France.; Laboratoire d'Excellence GR-Ex, Paris, France.; Institut National de la Transfusion Sanguine (INTS), Paris, France.; Discngine SAS, Paris, France., Narwani TJ; Biologie Intégrée du Globule Rouge UMR_S1134, Inserm, Univ. Paris, Univ. de la Réunion, Univ. des Antilles, Paris, France.; Laboratoire d'Excellence GR-Ex, Paris, France.; Institut National de la Transfusion Sanguine (INTS), Paris, France., Noël F; Biologie Intégrée du Globule Rouge UMR_S1134, Inserm, Univ. Paris, Univ. de la Réunion, Univ. des Antilles, Paris, France.; Laboratoire d'Excellence GR-Ex, Paris, France.; Institut National de la Transfusion Sanguine (INTS), Paris, France.; PSL Research University, INSERM, UMR 932, Institut Curie, Paris, France.; Université Paris Sud, Université Paris-Saclay, Orsay, France., Bertrand O; Biologie Intégrée du Globule Rouge UMR_S1134, Inserm, Univ. Paris, Univ. de la Réunion, Univ. des Antilles, Paris, France.; Laboratoire d'Excellence GR-Ex, Paris, France.; Institut National de la Transfusion Sanguine (INTS), Paris, France., Meyniel JP; ISoft, Saint-Aubin, France., Malpertuy A; Atragene, Ivry-sur-Seine, France., Gelly JC; Biologie Intégrée du Globule Rouge UMR_S1134, Inserm, Univ. Paris, Univ. de la Réunion, Univ. des Antilles, Paris, France.; Laboratoire d'Excellence GR-Ex, Paris, France.; Institut National de la Transfusion Sanguine (INTS), Paris, France.; IBL, Paris, France., Cadet F; Biologie Intégrée du Globule Rouge UMR_S1134, Inserm, Univ. Paris, Univ. de la Réunion, Univ. des Antilles, Paris, France.; Laboratoire d'Excellence GR-Ex, Paris, France.; Faculté des Sciences et Technologies, Saint Denis, La Réunion, France.; Peaccel, Protein Engineering Accelerator, Paris, France., de Brevern AG; Biologie Intégrée du Globule Rouge UMR_S1134, Inserm, Univ. Paris, Univ. de la Réunion, Univ. des Antilles, Paris, France.; Laboratoire d'Excellence GR-Ex, Paris, France.; Faculté des Sciences et Technologies, Saint Denis, La Réunion, France.; Institut National de la Transfusion Sanguine (INTS), Paris, France.; IBL, Paris, France.
Jazyk: angličtina
Zdroj: PeerJ [PeerJ] 2020 Mar 06; Vol. 8, pp. e8408. Date of Electronic Publication: 2020 Mar 06 (Print Publication: 2020).
DOI: 10.7717/peerj.8408
Abstrakt: Antigen binding by antibodies requires precise orientation of the complementarity- determining region (CDR) loops in the variable domain to establish the correct contact surface. Members of the family Camelidae have a modified form of immunoglobulin gamma (IgG) with only heavy chains, called Heavy Chain only Antibodies (HCAb). Antigen binding in HCAbs is mediated by only three CDR loops from the single variable domain (V H H) at the N-terminus of each heavy chain. This feature of the V H H, along with their other important features, e.g., easy expression, small size, thermo-stability and hydrophilicity, made them promising candidates for therapeutics and diagnostics. Thus, to design better V H H domains, it is important to thoroughly understand their sequence and structure characteristics and relationship. In this study, sequence characteristics of V H H domains have been analysed in depth, along with their structural features using innovative approaches, namely a structural alphabet. An elaborate summary of various studies proposing structural models of V H H domains showed diversity in the algorithms used. Finally, a case study to elucidate the differences in structural models from single and multiple templates is presented. In this case study, along with the above-mentioned aspects of V H H, an exciting view of various factors in structure prediction of V H H, like template framework selection, is also discussed.
Competing Interests: Frederic Cadet is associated with PEACCEL, Paris, France. Jean-Christophe Gelly and Alexandre G. de Brevern are associated with IBL, Paris, France. Jean-Philippe Meyneil is employed by ISoft, Paris, France. Alain Malpertuy is employed by Atragene, Paris, France. Nicolas K. Shinada is sponsored by Discngine, Paris, France and ANRT, France. All other authors declare no competing interests.
(©2020 Melarkode Vattekatte et al.)
Databáze: MEDLINE
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